Targeted　therapy　for　patients　with　hepatitis　B　virus　(HBV)　infection　can　lead　to　objective　responses,　although　response　times　may　be　short.　At　the　same　time,　the　response　rate　to　programmed　cell　death-1　(PD-1)　treatment　was　more　durable.　It　is　speculated　that　HBV　targeted　therapy　can　synergistically　enhance　the　antitumor　activity　with　PD-1　blockade.　To　test　this　hypothesis,　we　evaluated　the　effect　of　crispr-cas9　on　HBV　and　PD-1　in　vitro　and　in　vivo.　We　found　that　HBV　targeting　gRNA/cas9　induced　a　decrease　in　the　expression　of　HBsAg,　while　the　PD-1　gene　could　be　knocked　out　by　electroporation　targeting　gRNA　/　cas9　by　polymerase　chain　reaction.　In　HBV　transgenic　mice,　the　immunophenotype　and　cytokine　expression　of　human　dendritic　cells　(DCS)　were　detected　by　crispr-cas9　system　stimulation,　flow　cytometry　and　polymerase　chain　reaction.　These　results　indicate　that　gRNA/cas9　treatment　upregulates　the　expression　of　CD80,　CD83　and　CD86,　and　significantly　increases　the　mRNA　levels　of　IL-6,　IL-12,　IL-23　and　tumor　necrosis　factor　alpha.　The　combination　of　anti　HBV　and　anti　PD-1　therapy　can　inhibit　HBV　expression　and　significantly　improve　the　survival　of　HBV　transgenic　mice.　In　addition,　the　combination　therapy　increased　the　production　of　interferon　by　T　cells,　and　then　enhanced　the　expression　of　Th1　related　immunostimulatory　genes,　thereby　reducing　the　transcription　of　regulatory　/　inhibitory　immune　genes.　In　general,　this　response　can　reshape　the　tumor　microenvironment　from　immunosuppression　to　immune　stimulation.　Finally,　anti　HBV　therapy　can　induce　the　expression　of　interferon　dependent　programmed　cell　death　ligand-1　in　HBV　transgenic　mice　in　vivo.　To　sum　up,　these　results　demonstrate　that　the　combination　of　HBV　targeted　therapy　and　PD-1　immune　checkpoint　block　has　a　strong　synergistic　effect,　thus　supporting　the　transformation　potential　of　this　combined　therapy　strategy　in　clinical　treatment　of　HBV　infection.